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588 Background: Despite the use of multiple lines of targeted therapy has revolutionized treatment for HER2-positive breast cancer, these methods still have limited efficacy for triple-positive breast cancer (TPBC), which calls for persistent exploration for optimized treatment strategy. This MUKDEN-01 prospective trial aimed to evaluate the efficacy of oral, chemo-sparing neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib, which also meet the need for treatment convenience under COVID-19 pandemic, for patients with TPBC. Methods: The MUKDEN 01 was an investigator-initiated, multicentre, single arm, prospective phase II trial, which was performed at twelve hospitals in China(NCT04486911). Treatment-naïve patients with stage II-III tumors that according to the AJCC 8th edition criteria were eligible. Patients were treated with each cycle of 4 weeks with oral administration of pyrotinib 320 mg, and letrozole 2.5mg once daily for 4 weeks, and dalpiciclib 125 mg once daily for three weeks, followed by one week off, for five cycles. The primary endpoint was pathological complete response (pCR) in the breast and axilla (ypT0/is ypN0). Secondary endpoints included pCR in the breast (ypT0/is). residual cancer burden (RCB) score, Ki67 index change at surgery compared with baseline, and safety. Safety was analyzed in all patients, who received treatment. The study is still ongoing, and the enrollment has been completed. Results: Between June 20, 2020 and Sep. 6, 2021, 68 patients were screened for eligibility and 61 patients were recruited into this first stage of study. After surgery, 18 (29.5%, 95% CI 18.5-42.6) out of 61 patients achieving tpCR(ypT0/is ypN0), 21 (34.4%, 95% CI 22.7-47.7) patients achieved bpCR(ypT0/is). The patients with excellent pathologic response (RCB 0-1) to the combined therapy accounted for 54.1% (33/61, 95% CI 40.9-66.9). Mean Ki67 expression was reduced from 38.7% (95%CI: 31.3-46.0) at baseline to 19.3% (95% CI:13.6-25.0; p=0.0001) in the surgical samples. The most frequent grade 3 AE were neutropenia (35 [57%]), leukopenia (13 [21%]), diarrhea (9 [15%]) and oral mucositis (4 [7%]). There were five grade 4 neutropenia (8%) and one grade 4 increased AST (2%), but without other SAE and death throughout the study. Conclusions: Neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib yielded a pCR rate comparable to standard chemotherapy plus dual HER2 blockade in TPBC patients. The combined therapy was also well-tolerated and provided a chemo-sparing neoadjuvant approach for TPBC patients. To our knowledge, this is the first study to evaluate the therapeutic efficacy of a chemo-free neoadjuvant treatment with HER2 TKI pyrotinib and letrozole plus CDK4/6 inhibitor dalpiciclib for TPBC patients. Further validation in a large-scale randomized controlled trial is warranted. Clinical trial information: NCT04486911.

The present work involved a thorough study on silane-modified silica filler with special focus on its chemical interaction with polydimethylsiloxanes (PDMS) and the structural model of the modified filler. The samples prepared by addition of modified silica were characterized by Fourier transform infrared spectroscopy (FTIR), specific surface test, scanning electron microscopy (SEM) and fluorescent microscope. FTIR results confirmed the successful silica surface modification with silane coupling agent. The sample containing 80 phr (parts per hundreds of rubber) modified filler with weak ratio of Si–OH/Si–C group absorbance areas (A 1/A 0) showed weak formation of filler agglomerates while a stronger interfacial interaction could take place between the modified silica and PDMS. Specific surface results showed that the dispersion of silica can be improved when the amount of silane modifier to silica reached 2.0 wt%. SEM and fluorescent microscope showed that the filler aggregation was observed in cases of higher silica loading. As expected, when the silica with surface treatment was compared with those without surface modification, the filler particles were found to be fairly well dispersed in PDMS matrix.

Objective We studied the role of specific cytotoxic T lymphocytes (CTLs) activated by dendritic cells (DCs) presenting cationic nanoparticles with the K-ras (12-Val) mutant peptide and whole tumor antigen in the killing of different pancreatic cancer cell lines in vitro and in vitro.

Background The prognostic significance of FOXP3+ tumor-infiltrating lymphocytes (TILs) in patients with breast cancer remains controversial. The aims of our meta-analysis are to evaluate its association with clinicopathological characteristics and prognostic significance in patients with breast cancer. Methods PubMed, Embase, Cochrane Database and the Ovid Database were systematically searched (up to April 2015). The meta-analysis was performed using hazard ratio (HR), odds ratio (OR) and 95 % confidence intervals (CI) as effect measures. Using the random-effects model, statistical analysis was performed using Stata software, version 12.0. Results Seventeen studies including 8277 patients with breast cancer were analyzed. The meta-analysis indicated that the incidence difference of FOXP3+ TILs was significant when comparing the lymph node positive group to negative group (OR = 1.305, 95 % CI [1.071, 1.590]), the histological grade III group to the I–II group (OR = 3.067, 95 % CI [2.288, 4.111]), the ER positive group to the negative group (OR = 0.435, 95 % CI [0.287, 0.660]), the PR positive group to the negative group (OR = 0.493, 95 % CI [0.296, 0.822]), the HER2 positive group to the negative group (OR = 1.896, 95 % CI [1.335, 2.692]), the TNBC group to the non TNBC group (OR = 2.456, 95 % CI [1.801, 3.348]). The detection of FOXP3+ TILs was significantly correlated with the recurrence-free survival (RFS) of patients (HR = 1.752, 95 % CI [1.188–2.584]) and the overall survival (OS) of patients (HR =1.447, 95 % CI [1.037–2.019]). Conclusions Our meta-analysis demonstrates that the presence of high levels of FOXP3+ TILs is associated with prognosis for breast cancer patients and predicts lymph node metastasis, hormone receptor and HER-2 status.

to test the possible association between the polymorphism of Osteopontin (OPN) gene with the risk and the clinical features of papillary thyroid cancer (PTC).A total of 363 PTC patients and 413 healthy controls were enrolled. OPN expressions in tumor tissue were detected by immunohistochemistry. OPN gene polymorphisms, namely, -66TG (rs28357094), -156GGG (rs17524488), and -443CT (rs11730582), were determined.We observed that the PTC patients had significantly higher rates of -443TT genotypes than controls (P0.001). The multivariate logistic regression analysis showed a significantly increased risk for PTC for the -443CC genotype compared with the -443TT genotype (adjusted OR= 4.312, 95%CI: 2.747 -6.987, adjusted P0.001). OPN protein was not expressed in normal thyroid tissues while tumor samples from PTC patients were shown to have high expressions of OPN. Also, we found that the high OPN expressions were significantly more prevalent in -443CC carriers than TT carriers (P0.001). Both the CC carriers and OPN expression were closely associated with the cervical lymph node metastasis and angiolymphatic invasion of PTC.This study provides evidence to support the connection between the OPN genetic polymorphism and tissue expression with risk as well as the invasiveness of PTC.

The aim of this study was to investigate the role of specific cytotoxic T lymphocytes (CTLs) activated by dendritic cells (DCs) presenting cationic nanoparticles with the K-ras (12-Val) mutant peptide in the killing of different pancreatic cancer cell lines in vivo and in vitro. Peripheral blood DCs were induced by rhGM-CSF and IL-4 and cultured. DCs were sensitized by whole antigen of PANC-1 with expression of K-ras mutant, K-ras mutant peptide (K-ras+peptide) and cationic nanoparticles with K-ras mutant peptide (K-ras+peptide-CNP), respectively. Cell surface markers were measured by flow cytometry. Lymphocyte proliferation was detected by the 3H-TdR test, and IL-12 and IFN‑γ secretion was detected by ELISA. 125I-UdR was used to measure the killing effect of CTLs. The antitumor activity of CTLs in tumor-bearing nude mouse models prepared with PANC-1 and SW1990 cells was evaluated. Results showed that, compared with K-ras+peptide, low concentrations of K-ras+peptide-CNP were effectively presented by DCs (P0.05). CTLs induced by DCs pulsed with whole tumor antigen had a significantly greater killing effect (P0.05) on PANC-1 and SW1990 pancreatic cancer cells compared with K-ras+peptide- and K-ras+peptide-CNP-induced CTLs. CTLs induced by DCs pulsed with K-ras+peptide and K-ras+peptide- CNP had a specific killing effect (P0.05) on PANC-1 cells and no effect (P0.05) on SW1990 cells. In conclusion, cationic nanoparticles with the K-ras (12-Val) mutant peptide can be effectively presented by DCs at a low concentration. CTLs induced by K-ras+peptide-CNP had specific killing activity for the pancreatic cancer cell line with the K-ras mutant and significantly inhibited tumor growth and increased the survival time of tumor-bearing nude mice. Although this study confirmed that whole cell antigen induced a good antitumor immune response, the possibility of immune tolerance and autoimmunity which has been previously proven contribute to the difficulty in the application of this DC vaccine.